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secretion and
detection of K+ secretion in rectal biopsies from
cystic fibrosis patients
1 Universitäts-Kinderklinik, Albert-Ludwigs-Universität Freiburg, 79106 Freiburg; 2 Physiologisches Institut, Albert-Ludwigs-Universität Freiburg, 79104 Freiburg, Germany; and 3 Department of Physiology, University of Sydney, Sydney NSW 2006, Australia
Rectal biopsies
from cystic fibrosis (CF) patients show defective cAMP-activated
Cl
secretion and an inverse response of the
short-circuit current (Isc) toward stimulation with
carbachol (CCh). Alternative Cl channels are found
in airway epithelia and have been attributed to residual
Cl secretion in CF colon. The aim of the present
study was to investigate ion conductances causing reversed
Isc upon cholinergic stimulation. Furthermore, the
putative role of an alternative Ca2+-dependent
Cl conductance in human distal colon was examined.
Cholinergic ion secretion was assessed in the absence and presence of
cAMP-dependent stimulation. Transepithelial voltage and
Isc were measured in rectal biopsies from non-CF
and CF individuals by means of a perfused micro-Ussing chamber. Under
baseline conditions, CCh induced a positive Isc in
CF rectal biopsies but caused a negative Isc in non-CF subjects. The CCh-induced negative Isc in
non-CF biopsies was gradually reversed to a positive response by
incubating the biopsies in indomethacin. The positive
Isc was significantly enhanced in CF and was caused
by activation of a luminal K+ conductance, as shown by the
use of the K+ channel blockers Ba2+ and
tetraethylammonium. Moreover, a cAMP-dependent luminal K+
conductance was detected in CF individuals. We conclude that the cystic
fibrosis transmembrane conductance regulator is the predominant
Cl channel in human distal colon. Unlike human
airways, no evidence was found for an alternative Cl
conductance in native tissues from CF patients. Furthermore, we
demonstrated that both Ca2+- and cAMP-dependent
K+ secretion are present in human distal colon, which
are unmasked in rectal biopsies from CF patients.
cystic fibrosis transmembrane conductance regulator; human colon; epithelial transport; Ussing chamber
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